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Tumor necrosis factor expression during mouse hepatitis virus-induced demyelinating encephalomyelitis
S A Stohlman1, D R Hinton, D Cua
1Department of Neurology, University of Southern California School of Medicine, Los Angeles 90033, USA.
Journal of Virology
|September 1, 1995
Summary
Neutralizing antibodies against tumor necrosis factor alpha (TNF-alpha) did not prevent JHMV-induced encephalomyelitis or demyelination in mice. TNF-alpha was not secreted by infected cells, suggesting it does not contribute to disease.
Area of Science:
- Neuroimmunology
- Virology
- Molecular Biology
Background:
- Mouse hepatitis virus (JHMV) infection causes central nervous system (CNS) demyelination and encephalomyelitis.
- Tumor necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine implicated in various CNS diseases.
- The role of TNF-alpha in JHMV-induced pathology is not fully understood.
Purpose of the Study:
- To investigate the therapeutic potential of anti-TNF-alpha antibodies in JHMV infection.
- To determine the source and regulation of TNF-alpha during JHMV infection in the CNS.
Main Methods:
- Mice infected with JHMV were treated with neutralizing anti-TNF-alpha antibodies.
- Immunohistochemistry was used to detect JHMV and TNF-alpha in CNS tissues.
- In vitro studies assessed TNF-alpha mRNA and protein expression in JHMV-infected cells stimulated with lipopolysaccharide (LPS).
Main Results:
- Anti-TNF-alpha antibody treatment did not reduce JHMV-induced encephalomyelitis or demyelination.
- TNF-alpha-positive cells were observed in the CNS, but TNF-alpha did not colocalize with JHMV-infected cells.
- JHMV infection inhibited TNF-alpha secretion in vitro by blocking translation, despite rapid mRNA accumulation. Both live and inactivated JHMV inhibited LPS-induced TNF-alpha secretion.
Conclusions:
- TNF-alpha is not secreted by JHMV-infected cells.
- The lack of TNF-alpha secretion from infected cells suggests it does not play a significant role in JHMV-induced acute encephalomyelitis or primary demyelination.
- Targeting TNF-alpha may not be an effective therapeutic strategy for JHMV-induced CNS disease.